Hyperadrenal Disorders Flashcards
Describe the effects of excess cortisol on protein and fat synthesis.
Decrease protein synthesis
Increase fat synthesis
Explain why people with Cushing’s disease get stretch marks.
Put on a lot of fat quickly, which stretches the skin.
Because protein synthesis is switched off, can’t make the protein required for skin growth so the skin tears.
List 10 clinical features of Cushing’s syndrome.
Moon face Interscapular fat pad (buffalo hump) Proximal myopathy Centripetal obesity Easy bruising Striae Thin skin Osteoporosis Diabetes Hypertension + hypokalaemia
Why does Cushing’s syndrome cause hypertension and hypokalaemia?
At high concentrations, cortisol can have mineralocorticoid effects –> increased Na+ absorption + K+ excretion
State 4 causes of Cushing’s syndrome.
Excess steroid intake (glucocorticoids)
Pituitary dependent Cushing’s disease
Ectopic ACTH from lung cancer
Adrenal adenoma secreting cortisol
What are the 3 main tests used to diagnose Cushing’s syndrome?
24-hour collection for urine free cortisol
Blood diurnal cortisol levels (or midnight serum cortisol)
Low dose dexamethasone suppression test
Describe the results you’d expect from a normal subject and a patient with Cushing’s syndrome in the 24-hour urine free cortisol and blood diurnal cortisol tests.
Normal: lower cortisol at night + high cortisol in the morning.
Cushing’s: high cortisol all the time (problem- cortisol levels are affected by stress)
Explain the scientific basis of the low dose dexamethasone suppression test. Describe what you would see in a normal result and a Cushing’s result.
Dexamethasone is an artificial steroid so by giving this extra glucocorticoid, it should suppress ACTH + reduce cortisol production.
Normal: Suppress ACTH. Blood test = 0 cortisol
Cushing’s: Cortisol will remain high despite presence of dexamethasone.
State the surgical treatments for Cushing’s syndrome.
Dependent on cause:
Transsphenoidal Hypophysectomy (for Cushing’s disease)
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass
State 2 drugs that are used to treat Cushing’s syndrome before surgery.
Metyrapone
Ketoconazole
What is the problem with the low dose dexamethasone test?
It doesn’t tell you whether the issue is adrenal, pituitary or ectopic
Which enzyme is inhibited by metyrapone?
11-Beta-hydroxylase
What effect does metyrapone have on the steroid synthesis pathway?
Prevents conversion of:
11-deoxycorticosterone –> corticosterone
+
11-deoxycortisol –> cortisol
Thus, no corticosterone or cortisol is produced
State 2 uses of metyrapone.
Prep. Cushing’s patient for surgery (improves healing abilities + makes them better surgical candidates)
Control of Cushing’s symptoms after radiotherapy (radiotherapy has a delayed effect)
State 2 negative aspects of metyrapone.
- Causes accumulation of 11-deoxycorticosterone (because it doesn’t have negative feedback effects on ACTH axis)
11-deoxycorticosterone has mineralocorticoid effects so causes Na+ + water reabsorption, predisposing to HYPERTENSION. - Inhibits 2 limbs of the steroid synthesis pathway so funnels the precursors towards the sex steroid synthesis pathway.
This leads to increased adrenal androgens, which causes hirsuitism in women
What is ketoconazole and why is it no longer used?
An anti-fungal, which inhibits steroidogenesis.
No longer used because of its hepatotoxicity (except “off label” in prep for surgery)
What are the effects of ketoconazole on steroid production?
Ketoconazole inhibits enzyme which converts cholesterol to pregnenolone
So, it inhibits the production of glucocorticoids, mineralocorticoids + sex steroids.
State the main unwanted action of ketoconazole. How do we avoid this?
LIVER DAMAGE (possibly fatal) Monitor liver function weekly, clinically + biochemically
What is Conn’s syndrome?
Aldosterone secreting adenoma of the adrenal gland (zona glomerulosa)
What are the 2 main features of Conn’s syndrome?
Hypertension
Hypokalaemia
What is primary hyperaldosteronism?
Hyperaldosteronism caused by an adrenal adenoma.
What can you test to exclude secondary hyperaldosteronism?
Check for suppression of the renin-angiotensin system.
Conn’s: Aldosterone= high + Renin= suppressed (by high BP)
What is the usual treatment plan for someone with Conn’s syndrome?
Medical management (spironolactone) Surgery to remove the tumour
What is spironolactone and how does it work?
Spironolactone converted to Canrenone (a competitive mineralocorticoid receptor antagonist)
Blocks Na+ reabsorption + K+ excretion (K+ sparing diuretic)
